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Yamaguchi H.,Tohoku University | Shimada Y.,Asai Germanium Research Institute Co. | Shimada Y.,Iwate University | Takeda T.,Asai Germanium Research Institute Co. | And 2 more authors.
Analytical Chemistry | Year: 2015

Poly trans-[(2-carboxyethyl)germasesquioxane] (IUPAC name) is the most common water-soluble organic germanium compound. This compound is known as bis(carboxyethyl)germaniumsesquioxide and it is commonly called Ge-132; it is hydrolyzed to 3-(trihydroxygermyl)propanoic acid (THGPA) in water. We have developed a method for the quantification of THGPA in rat plasma, using a novel extraction method based on a reversible chemical conversion. THGPA in plasma is converted to 3-(trichlorogermyl)propanoic acid (TCGPA) under acidic conditions using concentrated hydrochloride, which is followed by extraction with chloroform. TCGPA is then converted back to THGPA through hydrolysis. The extraction recovery of this method is approximately 100%. Moreover, we synthesized deuterated Ge-132, which was used as an internal standard in our experiments. This method covers a linearity range of 0.01-5 μg/mL for concentrations of THGPA in plasma. The intra-day and inter-day precisions of the analysis are about 4.1%, and the accuracy is within ±2.6% at THGPA concentrations of 0.025, 0.25, and 2.5 μg/mL. The total run time is 5 min. Our method was successfully applied to a pharmacokinetic investigation following oral administration of Ge-132. © 2015 American Chemical Society.


Nakamura T.,Asai Germanium Research Institute Co. | Saito M.,Asai Germanium Research Institute Co. | Aso H.,Tohoku University
Bioscience, Biotechnology and Biochemistry | Year: 2012

The organic germanium compound, Ge-132, has immune-modulating effects. We evaluated the symbiotic effects of Ge-132 with lactobacilli and oligosaccharide (LB/OS) on the immune responses of mice. The highest fecal IgA levels were observed in the mice receiving a low concentration of Ge-132 with LB/OS for 8 weeks. Our data suggest that LB/OS with a low concentration of Ge-132 stimulated the intestinal immunity. © 2012 W. S. Maney & Son Ltd.


PubMed | Nippon Beet Sugar Manufacturing Co., Obihiro University of Agriculture and Veterinary Medicine and Asai Germanium Research Institute Co.
Type: Journal Article | Journal: Bioscience of microbiota, food and health | Year: 2014

Poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) is the most common organic germanium compound. The ingestion of Ge-132 promotes bile secretion. We assessed the rat caecal characteristics after the administration of Ge-132 and raffinose, a prebiotic oligosaccharide, because both Ge-132 and some prebiotics can change the fecal color to yellow. We also compared the changes in the caecal flora caused by the two compounds. In addition, we evaluated the simultaneous administration of Ge-132 and raffinose and their effects on -glucuronidase activity, which is known to be a factor related to colon cancer. Male Wistar rats (three weeks old) were given one of the following diets: 1) a control diet (control group), 2) a diet containing 0.05% Ge-132 (Ge-132 group), 3) a diet containing 5% raffinose (RAF group) or 4) a diet containing 0.05% Ge-132 + 5% raffinose (GeRAF group). The Bifidobacterium, Lactobacillus and total bacteria counts were significantly increased by the dietary raffinose, and Ge-132 did not suppress this increase. The raffinose intake increased caecal acetic acid production significantly. The activity of -glucuronidase in the caecal contents was increased by dietary Ge-132, whereas dietary raffinose decreased the -glucuronidase activity significantly. These results indicate that the simultaneous intake of dietary raffinose and Ge-132 does not inhibit the effects of either compound on intestinal fermentation and bile secretion. Additionally, the simultaneous intake of both raffinose and Ge-132 could abrogate the increase in -glucuronidase activity induced by Ge-132 alone.


Nakamura T.,Asai Germanium Research Institute Co. | Shimada Y.,Asai Germanium Research Institute Co. | Shimada Y.,Iwate University | Takeda T.,Asai Germanium Research Institute Co. | And 3 more authors.
Future Medicinal Chemistry | Year: 2015

In mammals, adrenaline and ATP are life-essential vicinal diol and cis-diol functional groups. Here, we show that interactions between a safe organogermanium compound and these cis-diol compounds have the potential to regulate physiological functions. In addition, we represent a possible new druggable target for controlling the action of cis-diol compounds. Results: We analyzed a single crystal structure of organogermanium 3-(trihydroxygermyl)propanoic acid (THGPA), a hydrolysate of safe Ge-132, in complex with catecholamine (adrenaline and noradrenaline), and evaluated the affinity between several cis-diol compounds and THGPA by NMR. An in vitro study using normal human epidermal keratinocytes was performed to investigate the inhibition of cis-diol compound-stimulated receptors by THGPA. At high concentration, THGPA inhibited the calcium influx caused by adrenaline and ATP. Conclusion: This study demonstrates that THGPA can modify cis-diol-mediated cell-to-cell signaling. © 2015 Future Science Ltd.


Nakamura T.,Asai Germanium Research Institute Co. | Saito M.,Asai Germanium Research Institute Co. | Shimada Y.,Asai Germanium Research Institute Co. | Fukaya H.,Tokyo University of Pharmacy and Life Science | And 2 more authors.
European Journal of Pharmacology | Year: 2011

Poly-trans-[(2-carboxyethyl) germasesquioxane], Ge-132 is a water-soluble organic germanium compound. Oral intake of dietary Ge-132 changes fecal color and we attempted to identify the fecal red pigment, which increased by the intake of dietary Ge-132. Sprague Dawley rats were given diets containing Ge-132 from 0 to 0.5% concentration. Fecal red pigment was extracted and purified for optical and structural studies. We examined the fecal red pigment content by high performance liquid chromatography (HPLC), and hepatic gene expressions relating to heme synthesis by reverse transcription polymerase chain reaction (RT-PCR). The purified red pigment had particular optical characteristics on the ultraviolet (UV)-visible spectrum (Soret band absorbance at 400 nm) and fluorescence emission at 600 nm by 400 nm excitation, and was identified as protoporphyrin IX by LC-MS analysis. Protoporphyrin IX significantly (P < 0.05) increased 2.4-fold in the feces by the intake of a 0.5% Ge-132 diet. Gene expression analysis of the liver explained the increase of protoporphyrin IX by dietary Ge-132 as it enhanced (P < 0.05) aminolevulinic acid synthase 1 (Alas1), a rate-limiting enzyme of heme synthesis, expression 1.8-fold, but decreased ferrochelatase (Fech) expression 0.6-fold (P < 0.05). The results show that the intake of dietary Ge-132 is related to heme metabolism. Because protoporphyrin IX is used to treat chronic hepatitis, Ge-132 may be a beneficial substance to increase protoporphyrin IX in the liver. © 2010 Elsevier B.V. All rights reserved.


Shimada Y.,Asai Germanium Research Institute Co. | Shimada Y.,Iwate University | Sato K.,Asai Germanium Research Institute Co. | Tokuji Y.,Iwate University | And 2 more authors.
Carbohydrate Research | Year: 2015

Poly-trans-[(2-carboxyethyl)germasesquioxane], Ge-132, is a water-soluble organic germanium compound with many reported physiological functions. The hydrolysate of Ge-132, 3-(trihydroxygermyl)propanoic acid, can interact with diol compounds; therefore, it can possibly interact with diol-containing sugar compounds, which have important physiological functions in sugar chains, glycoproteins, and glucolipids. In this study, we examined the interaction between sodium 3-(trihydroxygermyl)propanoate and monosaccharides using nuclear magnetic resonance. When 1,4-anhydroerythritol was mixed with sodium 3-(trihydroxygermyl)propanoate, a pattern of signals different from that obtained for each solute alone was observed. Some signals were broader, and novel signals with different chemical shifts appeared to originate from complex formation. Spectral observations for sodium 3-(trihydroxygermyl)propanoate and the sugar isomers of glucose and fructose indicated that sodium 3-(trihydroxygermyl)propanoate has a higher affinity for fructose (a ketose) than glucose (an aldose). Moreover, the β-furanosyl conformation of fructose was the structure that interacted most with sodium 3-(trihydroxygermyl)propanoate. These results demonstrate the ability of aqueous Ge-132 to form complexes with the cis-diol structures of saccharides. Thus, interactions among 3-(trihydroxygermyl)propanoic acid and the important biological sugar compounds might be implicated in the physiological function of Ge-132. © 2015 Elsevier Ltd. All rights reserved.


Nakamura T.,Asai Germanium Research Institute Co. | Takeda T.,Asai Germanium Research Institute Co. | Tokuji Y.,Obihiro University of Agriculture and Veterinary Medicine
International Journal for Vitamin and Nutrition Research | Year: 2015

The common water-soluble organic germanium compound poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) exhibits activities related to immune responses and antioxidant induction. In this study, we evaluated the antioxidative effect of dietary Ge-132 in the plasma of mice. Male ICR mice (seven mice per group) received an AIN-76 diet with 0.05 % Ge-132; three groups received the Ge-132-containing diet for 0, 1 or 4 days. The plasma alpha-tocopherol (α-tocopherol) concentration increased from 6.85 to 9.60 μg/ml after 4 days of Ge-132 intake (p < 0.05). We evaluated the changes in hepatic gene expression related to antioxidative activity as well as in the entire expression profile after one day of Ge-132 intake, using DNA microarray technology. We identified 1,220 genes with altered expression levels greater than 1.5-fold (increased or decreased) as a result of Ge-132 intake, and α-tocopherol transfer protein (Ttpa) gene expression was increased 1.62-fold. Immune activation was identified as the category with the most changes (containing 60 Gene Ontology (GO) term biological processes (BPs), 41 genes) via functional clustering analysis of altered gene expression. Ge-132 affected genes in clusters related to ATP production (22 GO term BPs, 21 genes), lipid metabolism (4 GO term BPs, 38 genes) and apoptosis (5 GO term BPs). Many GO term BPs containing these categories were significantly affected by the Ge-132 intake. Oral Ge-132 intake may therefore have increased plasma α-tocopherol levels by up-regulating α-tocopherol transfer protein (Ttpa) gene expression. © 2014 Hans Huber Publishers, Hogrefe AG, Bern.


Trademark
Asai Germanium Research Institute Co. | Date: 2015-11-22

Dietary and nutritional supplements containing germanium.


PubMed | Asai Germanium Research Institute Co
Type: Journal Article | Journal: Bioscience, biotechnology, and biochemistry | Year: 2012

The organic germanium compound, Ge-132, has immune-modulating effects. We evaluated the symbiotic effects of Ge-132 with lactobacilli and oligosaccharide (LB/OS) on the immune responses of mice. The highest fecal IgA levels were observed in the mice receiving a low concentration of Ge-132 with LB/OS for 8 weeks. Our data suggest that LB/OS with a low concentration of Ge-132 stimulated the intestinal immunity.


PubMed | Iwate University, Obihiro University of Agriculture and Veterinary Medicine and Asai Germanium Research Institute Co.
Type: | Journal: Carbohydrate research | Year: 2015

Poly-trans-[(2-carboxyethyl)germasesquioxane], Ge-132, is a water-soluble organic germanium compound with many reported physiological functions. The hydrolysate of Ge-132, 3-(trihydroxygermyl)propanoic acid, can interact with diol compounds; therefore, it can possibly interact with diol-containing sugar compounds, which have important physiological functions in sugar chains, glycoproteins, and glucolipids. In this study, we examined the interaction between sodium 3-(trihydroxygermyl)propanoate and monosaccharides using nuclear magnetic resonance. When 1,4-anhydroerythritol was mixed with sodium 3-(trihydroxygermyl)propanoate, a pattern of signals different from that obtained for each solute alone was observed. Some signals were broader, and novel signals with different chemical shifts appeared to originate from complex formation. Spectral observations for sodium 3-(trihydroxygermyl)propanoate and the sugar isomers of glucose and fructose indicated that sodium 3-(trihydroxygermyl)propanoate has a higher affinity for fructose (a ketose) than glucose (an aldose). Moreover, the -furanosyl conformation of fructose was the structure that interacted most with sodium 3-(trihydroxygermyl)propanoate. These results demonstrate the ability of aqueous Ge-132 to form complexes with the cis-diol structures of saccharides. Thus, interactions among 3-(trihydroxygermyl)propanoic acid and the important biological sugar compounds might be implicated in the physiological function of Ge-132.

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